Our research will confirm or refute earlier observations on the frequency and severity of depression following stroke as well as extend the understanding of the mechanisms of these disorders. Previous studies demonstrated that mood disorders meeting the DSM III or RDC symptom criteria for major depression or dysthymic depression occur in approximately 25% and 20% respectively of a relatively unselected population of stroke patients. The length of major depression appears to be approximately 1 year. The symptom cluster of major depression occurs significantly more often in patients with left anterior lesions as compared with any other lesion location and the proximity of the lesion to the frontal pole on CT scan correlates positively with the severity of depression. The depressions appear to be treatable with tricycylic antidepressants. The studies will improve on this preliminary work by including a more detailed evaluation of aphasia CT scan, neuropsychological deficits, life history of affective related disorders and their relationship to post-stroke mood disorders. In addition, spinal fluid metabolites will be examined to determine whether biogenic amine depletions correlate with lesion location and the existence or severity of depression. Family pedigrees will determine whether there is evidence for a genetic vulnerability to depression in the families of patients developing depression. The specificity of poststroke mood disorders will be examined by comparing them phenomenologically and longitudinally to mood changes in patients with myocardial infarctions or spinal cord injury. The response of depressive disorders and emotional lability to treatment with the tricyclic antidepressant, nortriptyline will be evaluated in double blind studies. The long term significance of this work is that some of the brain regions which play an important role in producing depression may be identified as well as providing a better understanding of the mechanisms, prognosis, and treatment of poststroke depression.